Session: OR33-Insulin Signaling & Inflammation
Room 303 (Moscone Center)
In this study we examined whether SAM supplementation affects HG mediated increase in TNF expression.
We used human CD14+ monocytes from healthy individuals and cultured them with normal (5.5mM) and high (25mM) glucose concentrations, with or without lipopolysaccharide (LPS, 100 ng/ml) in the presence or absence of SAM (0.25 to 0.75 mM). Effect of SAM on HG and LPS responsive TNFα and PDE4B mRNA and protein expression was assessed by real time PCR and ELISA. Histone modifications at the TNFα and PDE4B promoter regions were analyzed to determine potential role of epigenetic mechanisms in modulating cytokine responses.
The results obtained demonstrate that SAM significantly lowered high glucose and LPS-inducible PDE4B and consequently decreased TNFa expression. This phenomenon was the result of epigenetic changes involving histone modifications at the PDE4B and TNFα promoters leading to alterations in the relevant transcription factor binding (CREB and NFκB). These data identify PDE4 expression as a significant pathogenic component of high glucose and endotoxin mediated inflammation which can be targeted by SAM for the potential therapeutic use in the treatment of diseases characterized by elevated TNFa expression.
Nothing to Disclose: LG, DA, DM, CJM, SPLM, SSB
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